Cited by 20Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches

Xiong, Juan, Lu, Hui, Jiang, Yuanying·2025·ACS Infectious Diseases

Abstract

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster the efficacy of azole-based treatments. Drug repurposing stands as a promising and practical avenue for advancing antifungal therapy, with the potential for swift clinical translation. This review offers a comprehensive overview of azole synergistic agents uncovered through drug repurposing strategies, alongside an in-depth exploration of the mechanisms by which these agents augment azole potency. Drawing from these mechanisms, we delineate strategies aimed at enhancing azole effectiveness, such as inhibiting efflux pumps to elevate azole concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating fungal cell resistance to azoles, and disrupting biological processes extending beyond ergosterol synthesis. This review is beneficial for the development of these potentiators, as it meticulously examines instances and provides nuanced discussions on the mechanisms underlying the progression of azole potentiators through drug repurposing strategies.

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Crossref · 10.1021/acsinfecdis.4c00657

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Authors
Xiong, J., Lu, H., & Jiang, Y.
Affiliations
Tongji University (CN)
Corresponding author
  • Lu, Hui
  • Jiang, Yuanying
Venue
ACS Infectious Diseases
Published
2025-01-03
Volume
11
Issue
2
Pages
305-322
ISSN
2373-8227 (ISSN-L)
OpenAlex
W4406035076
Cited by
20
References
188
Citations by year
2026: 11 · 2025: 9
FWCI
3.50
Type
journal article
Language
en
Open access
closed
Locations
  • ACS Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Shanghai Municipal Education Commission (202101070007-E00094)
  • National Natural Science Foundation of China (82020108032)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
drug repurposing, azole resistance, fungal pathogens, antifungal therapy, efflux pump inhibition, ergosterol synthesis inhibition, fungal cell wall
MeSH terms
Antifungal Agents, Azoles, Drug Synergism, Fungi, Humans, Microbial Sensitivity Tests, Mycoses, Drug Resistance, Fungal, Drug Repositioning

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